Milciclib
Based on 7 publication(s) in Google Scholar
Milciclib (PHA-848125) is a potent, ATP-competitive and dual inhibitor of CDK and Tropomyosin receptor kinase (TRK), with IC50s of 45, 150, 160, 363, 398 nM and 53 nM for cyclin A/CDK2, cyclin H/CDK7, cyclin D1/CDK4, cyclin E/CDK2, cyclin B/CDK1 and TRKA, respectively.
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- Pureté : 99.57%
- CAS No.: 802539-81-7
- Formule: C25H32N8O
- Masse moléculaire:460.57
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Stockage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
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Solvant et solubilité
- Protocole
- Pureté et documentation
- Références
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Help & FAQs
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Publications Citing Use of MedChemExpress (MCE) Milciclib
More- Sci Transl Med. 2018 Jul 18;10(450):eaaq1093. [Abstract]
- J Exp Med. 2022 Jan 3;219(1):e20210789. [Abstract]
- Sci Rep. 2021 Mar 8;11(1):5374. [Abstract]
- Sci Rep. 2020 Jul 17;10(1):11921. [Abstract]
- Arch Pharm (Weinheim). 2024 Sep;357(9):e2400066. [Abstract]
- University of Washington. 2025.
- Technical University of Munich. 24.01.2018.
Activité biologique
Description
IC50 & Target
[1]|
cyclin A/CDK2 45 nM (IC50) |
cyclin E/CDK2 363 nM (IC50) |
cyclin H/CDK7 150 nM (IC50) |
cyclin D1/CDK4 160 nM (IC50) |
cyclin B/CDK1 398 nM (IC50) |
TRKA 53 nM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A2780 | IC50 |
0.2 μM
Compound: 28, PHA-848125
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Antiproliferative activity against human A2780 cells after 72 hrs by cell Titer_Glo assay
Antiproliferative activity against human A2780 cells after 72 hrs by cell Titer_Glo assay
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[PMID: 19603809] |
| HEK-293T | IC50 |
1.5 μM
Compound: Milciclib; PHA-848125
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Antiproliferative activity against HEK293T cells measured after 72 hrs by CellTiter-Blue assay
Antiproliferative activity against HEK293T cells measured after 72 hrs by CellTiter-Blue assay
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[PMID: 28792760] |
| HeLa | IC50 |
4 μM
Compound: 7; MMV676602
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Cytotoxicity against human HeLa cells assessed as reduction in cell viability after 48 hrs by resazurin dye based fluorescence assay
Cytotoxicity against human HeLa cells assessed as reduction in cell viability after 48 hrs by resazurin dye based fluorescence assay
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[PMID: 30647879] |
| MDA-MB-231 | IC50 |
0.31 μM
Compound: Milciclib; PHA-848125
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Antiproliferative activity against human MDA-MB-231 cells measured after 72 hrs by CellTiter-Blue assay
Antiproliferative activity against human MDA-MB-231 cells measured after 72 hrs by CellTiter-Blue assay
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[PMID: 28792760] |
| MDA-MB-231 | IC50 |
0.31 μM
Compound: 35
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Antiproliferative activity against human MDA-MB-231 cells
Antiproliferative activity against human MDA-MB-231 cells
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[PMID: 32688199] |
| MM1.S | IC50 |
0.72 μM
Compound: Milciclib; PHA-848125
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Antiproliferative activity against human MM1S cells measured after 72 hrs by CellTiter-Blue assay
Antiproliferative activity against human MM1S cells measured after 72 hrs by CellTiter-Blue assay
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[PMID: 28792760] |
| Sf9 | IC50 |
0.22 μM
Compound: Milciclib
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Inhibition of GST-tagged CDK4/cyclin D1 (unknown origin) expressed in Baculovirus infected Sf9 cells using RPPTLSPIPHIPR peptide as substrate in presence of [gamma-33P]-ATP by radiometric filter binding assay
Inhibition of GST-tagged CDK4/cyclin D1 (unknown origin) expressed in Baculovirus infected Sf9 cells using RPPTLSPIPHIPR peptide as substrate in presence of [gamma-33P]-ATP by radiometric filter binding assay
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[PMID: 30234987] |
| Sf9 | IC50 |
0.27 μM
Compound: Milciclib
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Inhibition of GST-tagged CDK7/cyclinH/MAT1 (unknown origin) expressed in Baculovirus infected Sf9 cells using YSPTSPS-2 KK peptide as substrate as substrate in presence of [gamma-33P]-ATP by radiometric filter binding assay
Inhibition of GST-tagged CDK7/cyclinH/MAT1 (unknown origin) expressed in Baculovirus infected Sf9 cells using YSPTSPS-2 KK peptide as substrate as substrate in presence of [gamma-33P]-ATP by radiometric filter binding assay
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[PMID: 30234987] |
| Sf9 | IC50 |
0.383 μM
Compound: Milciclib
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Inhibition of GST-tagged CDK5/p25 (unknown origin) expressed in Baculovirus infected Sf9 cells using histone H1 as substrate as substrate in presence of [gamma-33P]-ATP by radiometric filter binding assay
Inhibition of GST-tagged CDK5/p25 (unknown origin) expressed in Baculovirus infected Sf9 cells using histone H1 as substrate as substrate in presence of [gamma-33P]-ATP by radiometric filter binding assay
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[PMID: 30234987] |
| Sf9 | IC50 |
0.59 μM
Compound: Milciclib
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Inhibition of His-tagged CDK2/cyclin E (unknown origin) expressed in Baculovirus infected Sf9 cells using histone H1 as substrate in presence of [gamma-33P]-ATP by radiometric filter binding assay
Inhibition of His-tagged CDK2/cyclin E (unknown origin) expressed in Baculovirus infected Sf9 cells using histone H1 as substrate in presence of [gamma-33P]-ATP by radiometric filter binding assay
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[PMID: 30234987] |
| Sf9 | IC50 |
1.2 μM
Compound: Milciclib
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Inhibition of His-tagged CDK1/cyclin B1 (unknown origin) expressed in Baculovirus infected Sf9 cells using histone H1 as substrate in presence of [gamma-33P]-ATP by radiometric filter binding assay
Inhibition of His-tagged CDK1/cyclin B1 (unknown origin) expressed in Baculovirus infected Sf9 cells using histone H1 as substrate in presence of [gamma-33P]-ATP by radiometric filter binding assay
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[PMID: 30234987] |
| Sf9 | IC50 |
7.7 μM
Compound: Milciclib
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Inhibition of GST-tagged CDK9/CyclinT1 (unknown origin) expressed in Baculovirus infected Sf9 cells using YSPTSPS-2 KK peptide as substrate as substrate in presence of [gamma-33P]-ATP by radiometric filter binding assay
Inhibition of GST-tagged CDK9/CyclinT1 (unknown origin) expressed in Baculovirus infected Sf9 cells using YSPTSPS-2 KK peptide as substrate as substrate in presence of [gamma-33P]-ATP by radiometric filter binding assay
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[PMID: 30234987] |
In Vitro
Milciclib (PHA-848125; 0.156 or 0.625 μM) up-regulates the expression of PDCD4, DDIT4, SESN2/sestrin 2 and DEPDC6/DEPTOR in GL-Mel cells[1]. Milciclib (PHA-848125) potently inhibits the kinase activity of CDK2/cyclin A complex and of TRKA in a biochemical assay, with IC50s of 45 and 53 nM, respectively. Milciclib induces a clear accumulation of cells in G1 phase. Milciclib strongly inhibits NGF-induced phosphorylation of TRKA in a dose-dependent manner[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Essai clinique
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 802539-81-7
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Appearance Solid
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Masse moléculaire 460.57
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Formule C25H32N8O
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Color Light yellow to yellow
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SMILES
O=C(NC)C1=NN(C2=C1C(C)(CC3=CN=C(N=C23)NC4=CC=C(C=C4)N5CCN(CC5)C)C)C
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Synonyms
PHA-848125
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (7)
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Journal Impact Factor
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Most Recent
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Sci Transl Med
PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells. [Abstract]2018 Jul 18;10(450):eaaq1093. PMID: 30021885 -
J Exp Med
2022 Jan 3;219(1):e20210789. PMID: 34825915 -
Sci Rep
2021 Mar 8;11(1):5374. PMID: 33686114 -
Sci Rep
Analysis of the "centrosome-ome" identifies MCPH1 deletion as a cause of centrosome amplification in human cancer. [Abstract]2020 Jul 17;10(1):11921. PMID: 32681070 -
Arch Pharm (Weinheim)
Discovery of potent CSK inhibitors through integrated virtual screening and molecular dynamic simulation. [Abstract]2024 Sep;357(9):e2400066. PMID: 38809025 -
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Solvant et solubilité
In Vitro:
DMSO : 20 mg/mL (43.42 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2 mg/mL (4.34 mM); Clear solution
This protocol yields a clear solution of ≥ 2 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2 mg/mL (4.34 mM); Clear solution
This protocol yields a clear solution of ≥ 2 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocole
Cell Assay[2]
Cells are seeded into 96- or 384-well plates at densities ranging from 10,000 to 30,000/cm2 in appropriate medium plus 10% FCS. After 24 hours, cells are treated in duplicate with serial dilutions of Milciclib, and 72 hours later, viable cell number is assessed using the CellTiter-Glo Assay. IC50s are calculated using a Sigmoidal fitting algorithm. Experiments are done independently at least twice.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration[2]
Rats are randomized and introduced into the study when at least one mammary tumor attained a diameter of 0.5 cm. Groups of 10 animals are treated orally twice a day continuously for 10 days with vehicle (glucosate) or with 5, 10, and 15 mg/kg of Milciclib, whereas a further group receives two cycles of Milciclib at 20 mg/kg orally twice a day for 5 days with an intervening rest period of 1 week. Tumor volume is measured regularly by caliper for the duration of the experiment.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Pureté et documentation
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Fiche technique (279 KB)
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SDS (396 KB)
- English - EN (396 KB)
- Français - FR (396 KB)
- Deutsch - DE (396 KB)
- Norwegian - NO (396 KB)
- Español - ES (396 KB)
- Swedish - SV (396 KB)
- Italian - IT (396 KB)
- Korean - KR (396 KB)
- Portuguese - PT (396 KB)
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Instruction de manipulation (2659 KB)
Références
[1]. Caporali S, Alvino E, Levati L, Esposito AI, Ciomei M, Brasca MG, Del Bufalo D, Desideri M, Bonmassar E, Pfeffer U, D'Atri S. Down-regulation of the PTTG1 proto-oncogene contributes to the melanoma suppressive effects of the cyclin-dependent kinase inhibitor PHA-848125. Biochem Pharmacol. 2012 Sep 1;84(5):598-611. [Content Brief]
[2]. Albanese C, Alzani R, Amboldi N, Avanzi N, Ballinari D, Brasca MG, Festuccia C, Fiorentini F, Locatelli G, Pastori W, Patton V, Roletto F, Colotta F, Galvani A, Isacchi A, Moll J, Pesenti E, Mercurio C, Ciomei M. Dual targeting of CDK and tropomyosin receptor kinase families by the oral inhibitor PHA-848125, an agent with broad-spectrum antitumor efficacy. Mol Cancer Ther. 2010 Aug;9(8):2243-54. [Content Brief]
[3]. Degrassi A, et al. Efficacy of PHA-848125, a cyclin-dependent kinase inhibitor, on the K-Ras(G12D)LA2 lung adenocarcinoma transgenic mouse model: evaluation by multimodality imaging. Mol Cancer Ther. 2010 Mar;9(3):673-81. [Content Brief]
[4]. Brasca, M.G., et al. Identification of N,1,4,4-tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (PHA-848125), a potent, orally available cyclin dependent kinase inhibitor. J. Med. Chem. 52(16), 5152-5163 (2009). [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.1712 mL | 10.8561 mL | 21.7122 mL | 54.2806 mL |
| 5 mM | 0.4342 mL | 2.1712 mL | 4.3424 mL | 10.8561 mL | |
| 10 mM | 0.2171 mL | 1.0856 mL | 2.1712 mL | 5.4281 mL | |
| 15 mM | 0.1447 mL | 0.7237 mL | 1.4475 mL | 3.6187 mL | |
| 20 mM | 0.1086 mL | 0.5428 mL | 1.0856 mL | 2.7140 mL | |
| 25 mM | 0.0868 mL | 0.4342 mL | 0.8685 mL | 2.1712 mL | |
| 30 mM | 0.0724 mL | 0.3619 mL | 0.7237 mL | 1.8094 mL | |
| 40 mM | 0.0543 mL | 0.2714 mL | 0.5428 mL | 1.3570 mL |
Milciclib Related Classifications
HY-10424 Related Classifications
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